Significant role of Loss or Reduced BRCA1 gene expression in clinical implication of ovarian cancer

Abstract

Background: BRCA1 immunohistochemistry (IHC) provides a rapid initial screen to detect BRCA1 dysfunction in ovarian cancer that resulting from genetic alterations. Aim: To assess the expression of BRCA1 protein by IHC analysis among a group of Iraqi ovarian cancer patients to evaluate the patterns of expression and its correlation with the clinicopathological parameters in attempting to evaluate a significance role of BRCA1 gene implication in ovarian cancer. Methods: Forty three paraffin embedded samples of ovarian cancer cases were analyzed for BRCA1dysfunction by IHC analysis. The semi-quantitative approach using modified histochemical score (H-score) was achieved to assess the patterns of BRCA1 gene expression. Results: Complete loss of BRCA1 nuclear expression was detected in 30.2% of the cases while, reduced expression occurred in 46.5% of cases, giving rise to 76.7% of all cases detected with altered BRCA1 nuclear expression. Altered BRCA1 expression was found to be higher in age group ≤ 45 years (78.3%) in comparison with those of ages >45 years. Altered BRCA1 expression was significantly correlated with the high grade and with the unilateral tumor site when compared with the low grade and bilateral tumor site (P≤0.05), and was insignificantly correlated with the high stage ovarian tumors, 11.6% of cases were detected by cytoplasmic BRCA1 expression and no association was found between cytoplasmic expression and tumor grade, stage and tumor site. Conclusion: Altered BRCA1 expression may play a significant role in the progression of ovarian cancer. Recommendation: BRCA1 IHC is a clinically useful approach to detect the BRCA1 dysfunction and the H-score assessment reflects good estimation for BRCA1expression patterns.